Sleep is a natural, periodic behavioral state during which the body rests itself and its physiological powers are restored. It is characterized by a loss of reactivity to the environment. During sleep, certain physiological processes of both the body and the brain function differently than they do during alert wakefulness. Normal sleep consists of at least two quite different behavioral states: synchronized sleep, during which the electroencephalogram consists of slow waves of high amplitude, and desynchronized sleep (DS) or activated sleep characterized by rapid eye movements (REM sleep), in which the electroencephalogram pattern is characterized by waves of high frequency and low amplitude. Synchronized sleep is further characterized by slow and regular respiration, by relatively constant heart rate and blood pressure, and by a predominance of delta waves. Synchronized sleep usually consists of four stages, followed by a period of activated sleep. Each cycle lasts between 80 and 120 minutes. In contrast, desynchronized sleep is further characterized by irregular heart rate and respiration, periods of involuntary muscular jerks and movements, and a higher threshold for arousal. Periods of desynchronized sleep last from 5-20 minutes and occur at about 90 minute intervals during a normal night's sleep.
Sleep deprivation can arise from any of a variety of sleep disorders and environmental factors. Insomnia is a common sleep disorder in which the individual is unable to initiate or maintain sleep. In the prior art, there is no known pharmacological method for inducing the full sleep cycle and no known method using biological samples for assaying sleep deprivation.
Diagnosis and treatment of a sleep disorder can be assisted by a verification and/or quantification of a patient's level of sleep deprivation. Unfortunately, it is often difficult to objectively quantify or verify the level of sleep deprivation reported by a patient. What is needed is a biochemical product generated by the patient that can be correlated with sleep deprivation.
Cerebrospinal fluid (liquor cerebrosinalis) is a clear, colorless fluid that circulates within the four ventricles of the brain and the subarachnoid spaces surrounding the brain and spinal cord. Cerebrospinal fluid originates as an ultrafiltrate of the blood secreted by the choroid plexus in the lateral third and fourth ventricles. Cerebrospinal fluid is also sometimes called neurolymph. After passing through the four ventricles and the subarachnoid spaces, cerebrospinal fluid is largely resorbed into the venous system via the arachnoid villi. Cerebrospinal fluid serves as a medium for the removal of catabolites, excretions, and waste materials from the tissues bathed by it. To date, no factor derived from cerebrospinal fluid has been reported to correlate with sleep deprivation. What is needed is a method for analyzing cerebrospinal fluid for identifying a biochemical factor generated by subject that correlates with sleep deprivation.
Since the seminal discovery of prostaglandins, there has been increasing recognition of the role of fatty acids and their derivatives in important physiological processes, e.g., B. Samuelsson, Les Prix Nobel 1982, pp. 153-174.
Fatty acid primary amides have not been associated in the prior art with sleep induction or for assaying sleep deprivation. Fatty acid primary amides have been identified as an angiogenic principle from bovine mesentery. (K. Wakamatsu, T. Masaki, F. Itoh, K. Kondo, K. Sudo, Biochemical and Biophysical Research Communications (1990): vol. 168 (2), pages 423-429. Fatty acid primary amides have also been identified in human plasma without any attribution of function. (E. Arafat, J. W. Trimble, R. N. Andersen, C. Dass, D. M. Desiderio, Life Sciences (1989): vol. 45(18) pages 1679-1687).